Aging is associated with a decline in endothelial function which in-turn is a precursor to many adverse cardiovascular events. Numerous studies have shown that endurance exercise training enhances vascular function in both normal and aged humans and animals as well as under pathological conditions such as chronic heart failure, coronary artery disease, hypertension, hypercholesterolemia, obesity, and diabetes. Despite the evidence for exercise-induced improvements in vascular function in aged models, few of these studies have examined the effects of resistance training on vascular function. In addition, the few studies examining the effects of resistance training have primarily involved human subjects in which the molecular mechanisms of the improved endothelial function were not determined. One of the primary molecular mechanisms believed to play a role in endurance exercise induced improvement in vascular function is a decrease in superoxide formation and a concomitant increase in NO bioavailability. In light of these observations we will examine whether an 8 week resistance training program in rats will improve NO- dependent vasorelaxation in the aorta, femoral and resistance arterioles of aged animals using isolated vascular rings and cannulated, pressurized vessel preparations. Furthermore, we will examine changes in superoxide formation and protein tyrosine nitration in these vessels to determine if resistance exercise like endurance exercise reduces vascular oxidative stress. Potential cellular sources of superoxide generation and oxidative stress will also be explored using pharmacological inhibitors of superoxide and measures of superoxide formation. Finally, we will examine whether changes in eNOS expression or posttranslational modifications of eNOS can account for the improvements in endothelial function and reduction of oxidative stress in vessels from resistance trained, aged rats using co-immunoprecipitation and immunoblotting of these vascular tissues. Aim 1. To test the hypothesis that resistance exercise training will improve age-associated endothelial dysfunction in different vascular beds. Aim 2. To test the hypothesis that resistance exercise reduces vascular oxidative stress in young and old animals. Aim 3. To test the hypothesis that increases in NOS expression and posttranslational modifications of eNOS are transiently altered over the course of a chronic resistance exercise training program. PUBLIC HEALTH RELEVANCE: Cardiovascular disease is the leading cause of death in the United States and worldwide and the risk of having cardiovascular disease increases with age. Aging is also associated with a decline in muscular strength and mobility which can be prevented by resistance exercise training;however, it is unknown whether this type of training like endurance training can also reduce the risk of cardiovascular disease. This project will examine potential mechanisms by which resistance exercise training can reduce the risk of cardiovascular disease associated with advancing age.